{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:23:09Z","timestamp":1790760189189,"version":"4.1.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T00:00:00Z","timestamp":1516579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,2,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Previous studies localized the hedgehog (HH) signaling system to primary cilia. We discovered that motile cilia on airway epithelia also contain HH signaling proteins, indicating that like primary cilia, these motile cilia have an important sensory function. However, in contrast to the function of HH signaling in most primary cilia, sonic hedgehog (SHH) elicits noncanonical signaling, reducing cellular levels of cAMP. These findings suggest that airway SHH may quiet airway defenses. Involvement of SHH in lung disease and positioning of motile cilia where they sample SHH and other ligands in the airway lumen suggest that noncanonical HH signaling might modulate airway responses to the environment in health and disease.<\/jats:p>","DOI":"10.1073\/pnas.1719177115","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T15:07:07Z","timestamp":1516633627000},"page":"1370-1375","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling"],"prefix":"10.1073","volume":"115","author":[{"given":"Suifang","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Department of Molecular Physiology and Biophysics, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2916-9267","authenticated-orcid":false,"given":"Alok S.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Moninger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda S.","family":"Ostedgaard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Xiao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Thornell","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah R.","family":"Reznikov","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip H.","family":"Karp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaf","family":"Keshavjee","sequence":"additional","affiliation":[{"name":"Sprott Department of Surgery, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON MS5 1A1, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud H.","family":"Abou Alaiwa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Department of Molecular Physiology and Biophysics, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"},{"name":"Howard Hughes Medical Institute, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,1,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.3.2.207"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0328OC"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2774"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa5622"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.1.53"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70446-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02313"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/1717"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.08.035"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3598"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.08.019"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14984"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2016.11.010"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2016.04.001"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200709784"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1173869"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006031"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-010-0738-2"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01493"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00184.2012"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr569"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0132TR"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139740"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.217604"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04117"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200706028"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124534"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.69.040705.141236"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2011.11.002"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.074666"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/17611"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07459"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.082511"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018217108"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1602393113"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.14052"},{"key":"e_1_3_3_37_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1183\/09031936.93.04070789","article-title":"Effect of cyclic AMP on ciliary activity of human respiratory epithelium","volume":"4","author":"Di Benedetto G","year":"1991","unstructured":"G Di Benedetto, FS Manara-Shediac, A Mehta, Effect of cyclic AMP on ciliary activity of human respiratory epithelium. Eur Respir J 4, 789\u2013795 (1991).","journal-title":"Eur Respir J"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.S23"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604905113"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11130"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83922"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.10.015"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910712107"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-9-49"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.3.10591"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.01.033"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(08)00809-0"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708321114"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.243402"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912180106"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21142"},{"key":"e_1_3_3_52_2","doi-asserted-by":"crossref","first-page":"e0140886","DOI":"10.1371\/journal.pone.0140886","article-title":"Sonic hedgehog signaling: Evidence for its protective role in endotoxin induced acute lung injury in mouse model","volume":"10","author":"Chen X","year":"2015","unstructured":"X Chen, Y Jin, X Hou, F Liu, Y Wang, Sonic hedgehog signaling: Evidence for its protective role in endotoxin induced acute lung injury in mouse model. PLoS One 10, e0140886 (2015).","journal-title":"PLoS One"},{"key":"e_1_3_3_53_2","first-page":"115","article-title":"An in vitro model of differentiated human airway epithelia. Methods for establishing primary cultures","volume":"188","author":"Karp PH","year":"2002","unstructured":"PH Karp, , An in vitro model of differentiated human airway epithelia. Methods for establishing primary cultures. Methods Mol Biol 188, 115\u2013137 (2002).","journal-title":"Methods Mol Biol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1719177115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T13:09:36Z","timestamp":1693487376000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1719177115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,22]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,2,6]]}},"alternative-id":["10.1073\/pnas.1719177115"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1719177115","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,22]]},"assertion":[{"value":"2018-01-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}